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Clinical Trial Results:
LY2216684 Compared to Placebo as Adjunctive Therapy to SSRI in the Prevention of Symptom Re-emergence in Major Depressive Disorder

Summary
EudraCT number	2010-024632-42
Trial protocol	DE BE SK GR ES IT
Global end of trial date	14 Nov 2013

Results information
Results version number	v1(current)
This version publication date	06 Mar 2018
First version publication date	06 Mar 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

H9P-MC-LNBN

ISRCTN number

US NCT number

NCT01299272

WHO universal trial number (UTN)

Other trial identifiers

Trial Alias: 14310

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon-Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-CTLilly,

Scientific contact

Available Mon-Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-285-4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

14 Nov 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Nov 2013

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to assess the maintenance of efficacy of LY2216684 compared with placebo as adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) as measured by the time-to-symptom reemergence among participants with major depressive disorder (MDD) who met randomization criteria with adjunctive LY2216684 during the stabilization period.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

SSRI: Participants were treated with one of the following SSRIs that has been approved for MDD treatment within the participating country: escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine; and has been treated with their SSRI at least 6 weeks prior to Visit 2 with at least the last 4 consecutive weeks at a stable optimized dose prior to Visit 2. The SSRI prescribed, including dose, should be consistent with labeling guidelines within the participating country.

Evidence for comparator

Actual start date of recruitment

12 May 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 11

Country: Number of subjects enrolled

Argentina: 62

Country: Number of subjects enrolled

Croatia: 9

Country: Number of subjects enrolled

France: 61

Country: Number of subjects enrolled

Germany: 73

Country: Number of subjects enrolled

Greece: 43

Country: Number of subjects enrolled

Italy: 44

Country: Number of subjects enrolled

Korea, Republic of: 18

Country: Number of subjects enrolled

Mexico: 63

Country: Number of subjects enrolled

Puerto Rico: 77

Country: Number of subjects enrolled

Romania: 19

Country: Number of subjects enrolled

Russian Federation: 96

Country: Number of subjects enrolled

Slovakia: 65

Country: Number of subjects enrolled

Spain: 43

Country: Number of subjects enrolled

Turkey: 30

Country: Number of subjects enrolled

United States: 535

Worldwide total number of subjects

1249

EEA total number of subjects

368

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1175

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

All enrolled participants entered the Acute Open-label (OL) Period. At Week 8, if remission criteria were met, participants entered the Stabilization OL Period. At Week 20, if randomization criteria were met, participants entered the 24-week Double-blind Randomized Withdrawal Period. Those who discontinued early entered the Discontinuation Period.

Period 1 title

Acute open-label (OL) period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

LY2216684 + SSRI (Acute open-label period)

Arm description

Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Arm type

Experimental

Investigational medicinal product name

LY2216684

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a selective serotonin SSRI.

Number of subjects in period 1	LY2216684 + SSRI (Acute open-label period)
Started	1249
Entered Discontinuation (DC) Period	271 ^[1]
Completed	835
Not completed	414
Consent withdrawn by subject	56
Physician decision	5
Adverse event, non-fatal	140
Sponsor Decision	13
Lost to follow-up	14
Remission Criteria Not Met	140
Protocol deviation	36
Lack of efficacy	10

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who discontinued the Acute OL Period had the option to enter the DC Period.

Period 2 title

stabilization open-label (OL) period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

LY2216684 + SSRI (stabilization open-label period)

Arm description

Arm type

Experimental

Investigational medicinal product name

LY2216684

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2	LY2216684 + SSRI (stabilization open-label period)
Started	835
Entered Discontinuation (DC) Period	164 ^[2]
Completed	586
Not completed	249
Consent withdrawn by subject	42
Physician decision	3
Adverse event, non-fatal	42
Sponsor Decision	12
Randomization Criteria Not Met	80
Reemergence of Study Condition Symptoms	6
Lost to follow-up	9
Protocol deviation	44
Lack of efficacy	11

Notes
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who discontinued the Stabilization OL Period had the option to enter the DC Period.

Period 3 title

Double-blind (DB) Randomized Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)

Arm description

Flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a SSRI. At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks.

Arm type

Experimental

Investigational medicinal product name

LY2216684

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Placebo + SSRI (Double-blind Randomized Withdrawal Period)

Arm description

Flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a SSRI. At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a SSRI. At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.

Number of subjects in period 3	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Started	294	292
Entered Taper Discontinuation Period	129 ^[3]	0 ^[4]
Entered Abrupt Discontinuation Period	132 ^[5]	268
Completed	224	234
Not completed	70	58
Consent withdrawn by subject	22	15
Physician decision	2	1
Adverse event, non-fatal	8	9
Sponsor Decision	1	1
Reemergence of Study Condition Symptoms	4	10
Lost to follow-up	5	5
Lack of efficacy	20	10
Protocol deviation	8	7

Notes
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed or discontinued the DB Period were randomized to the taper DC Period.Participants who completed or discontinued the DB Period were randomized to the abrupt DC Period.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed or discontinued the DB Period entered the DC Period.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants who completed or discontinued the DB Period were randomized to the taper DC Period. Participants who completed or discontinued the DB Period were randomized to the abrupt DC Period.

Baseline characteristics

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Reporting group title

Acute open-label (OL) period

Reporting group description

All enrolled participants.

Reporting group values	Acute open-label (OL) period	Total
Number of subjects	1249	1249
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	47.4 ( 12.54 )	-
Gender, Male/Female
Units: Participants
Female	917	917
Male	332	332
Region of Enrollment
Units: Subjects
United States	535	535
Slovakia	65	65
Greece	43	43
Spain	43	43
Turkey	30	30
Russian Federation	96	96
Italy	44	44
France	61	61
Mexico	63	63
Puerto Rico	77	77
Argentina	62	62
Belgium	11	11
Croatia	9	9
Romania	19	19
Germany	73	73
Korea, Republic of	18	18
Race
Units: Subjects
American Indian or Alaska Native	50	50
Asian	21	21
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	99	99
White	1066	1066
More than one race	13	13
Unknown or Not Reported	0	0
Ethnicity
Units: Subjects
Hispanic or Latino	254	254
Not Hispanic or Latino	622	622
Unknown or Not Reported	373	373

End points

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Reporting group title

LY2216684 + SSRI (Acute open-label period)

Reporting group description

Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI).

Reporting group title

LY2216684 + SSRI (stabilization open-label period)

Reporting group description

Reporting group title

LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)

Reporting group description

Reporting group title

Placebo + SSRI (Double-blind Randomized Withdrawal Period)

Reporting group description

Flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a SSRI. At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for 12 weeks. At 20 weeks, participants meeting criteria for randomization were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.

Subject analysis set title

All Enrolled Participants

Subject analysis set type

Full analysis

Subject analysis set description

All enrolled participants started on a flexible dose of 12 or 18 mg LY2216684, administered orally, QD for 8 weeks, adjunctive to a SSRI. At 8 weeks, participants meeting remission criteria continued on the same, stable dose of LY2216684 and SSRI, orally, QD, for an additional 12 weeks. At 20 weeks, participants meeting criteria for randomization either 1) continued at their current dose of LY2216684 and SSRI, orally, QD, for an additional 24 weeks or 2) were switched from LY2216684 to Placebo and continued at their current SSRI dose, orally, QD, for an additional 24 weeks.

Primary: Percentage of Participants who meet criteria for re-emergence of depressive symptoms estimated by Kaplan-Meier product limit method (Double-blind Randomized Withdrawal Period)

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End point title

Percentage of Participants who meet criteria for re-emergence of depressive symptoms estimated by Kaplan-Meier product limit method (Double-blind Randomized Withdrawal Period)

End point description

Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. Time from randomization to the first visit at which the participant met the reemergence criteria was calculated. The percentage of participants who meet criteria was estimated using the Kaplan-Meier product limit method. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).

End point type

Primary

End point timeframe

Randomization up to 44 weeks

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	294 ^[1]	292 ^[2]
Units: percentage of participants
number (not applicable)	10.43	8.24

Notes
[1] - All randomized participants.
[2] - All randomized participants.

Statistical Analysis 1

Comparison groups

LY2216684 + SSRI (Double-blind Randomized Withdrawal Period) v Placebo + SSRI (Double-blind Randomized Withdrawal Period)

Number of subjects included in analysis

586

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.485

Method

Logrank

Confidence interval

Secondary: Percentage of participants with re-emergence of depressive symptoms (Double-blind Randomized Withdrawal Period)

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End point title

Percentage of participants with re-emergence of depressive symptoms (Double-blind Randomized Withdrawal Period)

End point description

Participants meeting any of the following criteria were determined as having major depressive disorder symptom re-emergence: 1) a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater ≥14 or a Clinical Global Impressions of Severity (CGI-S) increase of 2 or more points from Week 18 at 2 consecutive visits or 2) discontinuation due to lack of efficacy/worsening of depression/suicidality. The percentage of participants with re-emergence of depressive symptoms was calculated by dividing the number of participants who meet any of the criteria by the total number of participants analyzed, multiplied by 100. The MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity) to 60 (high severity). CGI-S measures severity of depression at the time of assessment compared with the start of treatment. Scores range from 1 (normal, not at all ill) to 7 (extremely ill).

End point type

Secondary

End point timeframe

Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	294 ^[3]	292 ^[4]
Units: percentage of participants
number (not applicable)	9.9	8.2

Notes
[3] - All randomized participants.
[4] - All randomized participants.

No statistical analyses for this end point

Secondary: Change from randomization in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores at Week 44 (double-blind randomized withdrawal period)

End point description

The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a 'significant' case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal'. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline subscale score and baseline subscale score-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	286	285
Units: units on a scale
least squares mean (standard error)
HADS Anxiety Subscale Score	0 ( 0.22 )	0.15 ( 0.22 )
HADS Depression Subscale Score	-0.18 ( 0.23 )	0.15 ( 0.23 )

No statistical analyses for this end point

Secondary: Change from randomization in the Clinical Global Impression of Severity (CGI-S) scores at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Clinical Global Impression of Severity (CGI-S) scores at Week 44 (double-blind randomized withdrawal period)

End point description

The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CGI-S score and baseline CGI-S score-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	290	292
Units: units on a scale
least squares mean (standard error)	0.01 ( 0.05 )	0 ( 0.05 )

No statistical analyses for this end point

Secondary: Change from randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores at week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores at week 44 (double-blind randomized withdrawal period)

End point description

MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which includes terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline MADRS total score (individual item score) and baseline MADRS total score (individual item score)-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	290	292
Units: units on a scale
least squares mean (standard error)
MADRS Total Score	0.4 ( 0.33 )	0.34 ( 0.33 )
Item 1: Apparent Sadness	0.09 ( 0.05 )	0.08 ( 0.05 )
Item 2: Reported Sadness	0.09 ( 0.06 )	0.05 ( 0.06 )
Item 3: Inner Tension	0.06 ( 0.07 )	0.14 ( 0.06 )
Item 4: Reduced Sleep	-0.02 ( 0.07 )	-0.06 ( 0.07 )
Item 5: Reduced Appetite	0 ( 0.04 )	0 ( 0.04 )
Item 6: Concentration Difficulties	0.07 ( 0.06 )	0.08 ( 0.06 )
Item 7: Lassitude	0.02 ( 0.06 )	0.07 ( 0.06 )
Item 8: Inability to Feel	0 ( 0.05 )	-0.05 ( 0.05 )
Item 9: Pessimistic Thoughts	-0.01 ( 0.05 )	-0.02 ( 0.04 )
Item 10: Suicidal Thoughts	0.02 ( 0.02 )	0.01 ( 0.02 )

No statistical analyses for this end point

Secondary: Change from randomization in the Sheehan Disability Scale (SDS) items at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Sheehan Disability Scale (SDS) items at Week 44 (double-blind randomized withdrawal period)

End point description

The Sheehan Disability Scale (SDS) is completed by the participant and used to assess the effect of the participant's symptoms on their work (work/school impairment score), social life (social life/leisure activities impairment score), and family life (family life/home responsibilities impairment score). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	289	289
Units: units on a scale
least squares mean (standard error)
Work Impairment Score (n=198, 212)	-0.24 ( 0.17 )	0.02 ( 0.17 )
Social Life Impairment Score (n=286, 286)	-0.17 ( 0.14 )	-0.15 ( 0.14 )
Family Life Impairment Score (n=286, 286)	-0.26 ( 0.14 )	-0.08 ( 0.14 )

No statistical analyses for this end point

Secondary: Change from randomization in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score at Week 44 (double-blind randomized withdrawal period)

End point description

The FAsD is a 13-item participant-rated scale.Items 1-6 ask how often participants(pts) experience different aspects of fatigue with responses from 1(never) to 5(always).Items 7-13 ask how often fatigue impacts various aspects of pts lives with responses from 1(not at all) to 5(very much).The experience subscale score is derived by taking mean of Items 1-6.The impact subscale score is derived by taking mean of applicable Items 7-13.The average score is mean of applicable Items 1-13.Item 12 applies only to pts with a spouse or significant other and Item 13 applies to pts who had job or went to school. LS means were calculated using a MMRM analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	286 ^[5]	286 ^[6]
Units: units on a scale
least squares mean (standard error)
FAsD Experience Subscale Score	-0.05 ( 0.05 )	0.05 ( 0.05 )
FAsD Impact Subscale Score	-0.06 ( 0.05 )	-0.01 ( 0.05 )
FAsD Average Score	-0.05 ( 0.05 )	0.02 ( 0.05 )

Notes
[5] - Participants with non-missing values at time of randomization, at least one post-randomization value
[6] - Participants with non-missing values at time of randomization, at least one post-randomization value

No statistical analyses for this end point

Secondary: Change from randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (double-blind randomized withdrawal period)

End point description

Arizona Sexual Experiences (ASEX) Questionnaire is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each item is rated from 1 (extremely) to 6 (no/never). Possible total scores ranged from 5 to 30, with the higher scores indicating more sexual dysfunction. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline ASEX total score and baseline ASEX total score-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	280	277
Units: units on a scale
least squares mean (standard error)	-0.39 ( 0.33 )	-0.08 ( 0.33 )

No statistical analyses for this end point

Secondary: Change from randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 44 (double-blind randomized withdrawal period)

End point description

The profile allows participants(pts) to rate their health state in 5 health domains: mobility,self-care,usual activities,pain/discomfort,and mood using a 3-level scale(no problem,some problems, and major problems).These dimensions are converted into weighted health-state index scores according to United States(US),United Kingdom(UK) population-based algorithms.The US and UK based index scores range from -0.11 to 1.0(where score of 1.0 indicates perfect health)and from -0.59(severe problems in all 5 dimensions) to 1.0(no problem in any dimension)respectively.The VAS consists of pts rating their current health state from 0(worst imaginable health state) to 100(best imaginable health).LS means calculated using analysis of ANCOVA model with main effects of treatment,country,baseline score.Analysis population included all randomized pts who have non-missing values at time of randomization and at least one post-randomization value.Last observation carried forward(LOCF) methodology was used.

End point type

Secondary

End point timeframe

Randomization, up to Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	278	285
Units: units on a scale
least squares mean (standard error)
EQ-5D US (n=278, 284)	0.01 ( 0.01 )	0.01 ( 0.01 )
EQ-5D UK (n=278, 284)	0.01 ( 0.02 )	0.01 ( 0.02 )
VAS (n=278, 285)	1.87 ( 1.39 )	0.61 ( 1.39 )

No statistical analyses for this end point

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (double-blind randomized withdrawal period)

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End point title

Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (double-blind randomized withdrawal period)

End point description

The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization through Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	291	292
Units: participants
number (not applicable)
TE Suicidal Ideation (n=291, 292)	5	4
TE Suicidal Behavior (n=277, 278)	1	0

No statistical analyses for this end point

Secondary: Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 8 (acute open-label period)

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End point title

Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 8 (acute open-label period)

End point description

Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Analysis population included all randomized participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Baseline, up to Week 8

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1214
Units: units on a scale
arithmetic mean (standard deviation)
MADRS Total Score	-13.21 ( 8.3 )
Item 1: Apparent Sadness	-1.82 ( 1.37 )
Item 2: Reported Sadness	-1.86 ( 1.39 )
Item 3: Inner Tension	-1.24 ( 1.37 )
Item 4: Reduced Sleep	-1.29 ( 1.57 )
Item 5: Reduced Appetite	-0.65 ( 1.47 )
Item 6: Concentration Difficulties	-1.49 ( 1.43 )
Item 7: Lassitude	-1.74 ( 1.44 )
Item 8: Inability to Feel	-1.65 ( 1.42 )
Item 9: Pessimistic Thoughts	-1.23 ( 1.28 )
Item 10: Suicidal Thoughts	-0.24 ( 0.7 )

No statistical analyses for this end point

Secondary: Change from Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 20 (stabilization open-label period)

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End point title

Change from Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 20 (stabilization open-label period)

End point description

Montgomery-Asberg Depression Rating Scale (MADRS) is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist (sadness [apparent], sadness [reported], inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Analysis population included all randomized participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Week 8, up to Week 20

End point values	LY2216684 + SSRI (stabilization open-label period)
Number of subjects analysed	812
Units: units on a scale
arithmetic mean (standard deviation)
MADRS Total Score	-0.38 ( 6.09 )
Item 1: Apparent Sadness	-0.01 ( 1.01 )
Item 2: Reported Sadness	-0.08 ( 1.15 )
Item 3: Inner Tension	-0.05 ( 1.18 )
Item 4: Reduced Sleep	-0.12 ( 1.28 )
Item 5: Reduced Appetite	0 ( 0.89 )
Item 6: Concentration Difficulties	-0.06 ( 1.19 )
Item 7: Lassitude	0.02 ( 1.19 )
Item 8: Inability to Feel	-0.09 ( 1.08 )
Item 9: Pessimistic Thoughts	-0.04 ( 0.87 )
Item 10: Suicidal Thoughts	0.03 ( 0.47 )

No statistical analyses for this end point

Secondary: Change from randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 44 (double-blind randomized withdrawal period)

End point description

Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score is reported and ranges from 7 to 42, with higher scores indicating greater impairment. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline CPFQ total score and baseline CPFQ total score-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	286	286
Units: units on a scale
least squares mean (standard error)	-0.27 ( 0.31 )	-0.05 ( 0.31 )

No statistical analyses for this end point

Secondary: Change from Week 8 in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 20 (stabilization open-label period)

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End point title

Change from Week 8 in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 20 (stabilization open-label period)

End point description

End point type

Secondary

End point timeframe

Week 8, up to Week 20

End point values	LY2216684 + SSRI (stabilization open-label period)
Number of subjects analysed	781
Units: units on a scale
arithmetic mean (standard deviation)
HADS Anxiety Subscale Score	-0.77 ( 3.73 )
HADS Depression Subscale Score	-0.74 ( 3.57 )

No statistical analyses for this end point

Secondary: Change from baseline in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 8 (acute open-label period)

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End point title

Change from baseline in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 8 (acute open-label period)

End point description

End point type

Secondary

End point timeframe

Baseline, up to Week 8

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1199
Units: units on a scale
arithmetic mean (standard deviation)
HADS Anxiety Subscale Score (n=1198)	-3.02 ( 3.92 )
HADS Depression Subscale Score (n=1199)	-3.98 ( 4.41 )

No statistical analyses for this end point

Secondary: Change from baseline in the Clinical Global Impression of Severity (CGI-S) scores up to Week 8 (acute open-label period)

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End point title

Change from baseline in the Clinical Global Impression of Severity (CGI-S) scores up to Week 8 (acute open-label period)

End point description

The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Analysis population included all randomized participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Baseline, up to Week 8

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1214
Units: units on a scale
arithmetic mean (standard deviation)	-1.51 ( 1.17 )

No statistical analyses for this end point

Secondary: Change from Week 8 in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 20 (stabilization open-label period)

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End point title

Change from Week 8 in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 20 (stabilization open-label period)

End point description

The Fatigue Associated with Depression (FAsD) is a 13-item participant-rated scale. Items 1-6 ask how often participants experience different aspects of fatigue with responses from 1 (never) to 5 (always). Items 7-13 ask how often fatigue impacts various aspects of the participant's lives with responses from 1 (not at all) to 5 (very much). The experience subscale score is derived by taking the mean of Items 1-6. The impact subscale score is derived by taking the mean of applicable Items 7-13. The average score is the mean of applicable Items 1-13. Item 12 applies only to participants with a spouse or significant other and Item 13 applies to participants who had a job or who went to school. Analysis population included all randomized participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Week 8, up to Week 20

End point values	LY2216684 + SSRI (stabilization open-label period)
Number of subjects analysed	781
Units: units on a scale
arithmetic mean (standard deviation)
FAsD Experience Subscale Score	-0.22 ( 0.93 )
FAsD Impact Subscale Score	-0.15 ( 0.87 )
FAsD Average Score	-0.19 ( 0.84 )

No statistical analyses for this end point

Secondary: Change from Week 8 in the Clinical Global Impression of Severity (CGI-S) scores up to Week 20 (stabilization open-label period)

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End point title

Change from Week 8 in the Clinical Global Impression of Severity (CGI-S) scores up to Week 20 (stabilization open-label period)

End point description

The Clinical Global Impression of Severity (CGI-S) instrument is used to record the severity of mental illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Analysis population included all randomized participants who have non-missing values at Week 8 and at least one post-Week 8 value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Week 8, up to Week 20

End point values	LY2216684 + SSRI (stabilization open-label period)
Number of subjects analysed	812
Units: units on a scale
arithmetic mean (standard deviation)	-0.25 ( 0.95 )

No statistical analyses for this end point

Secondary: Change from Baseline in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 8 (acute open-label period)

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End point title

Change from Baseline in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 8 (acute open-label period)

End point description

The FAsD is a 13-item participant-rated scale.Items 1-6 ask how often participants(pts) experience different aspects of fatigue with responses from 1(never) to 5(always).Items 7-13 ask how often fatigue impacts various aspects of pts lives with responses from 1(not at all) to 5(very much).The experience subscale score is derived by taking mean of Items 1-6.The impact subscale score is derived by taking mean of applicable Items 7-13.The average score is mean of applicable Items 1-13.Item 12 applies only to pts with a spouse or significant other and Item 13 applies to pts who had job or went to school. Analysis population included all randomized participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Baseline, up to Week 8

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1166
Units: units on a scale
arithmetic mean (standard deviation)
FAsD Experience Subscale Score (n=1166)	-0.82 ( 0.99 )
FAsD Impact Subscale Score (n=1164)	-0.88 ( 1.03 )
FAsD Average Score (n=1164)	-0.85 ( 0.93 )

No statistical analyses for this end point

Secondary: Change from baseline in the Sheehan Disability Scale (SDS) items up to Week 8 (acute open-label period)

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End point title

Change from baseline in the Sheehan Disability Scale (SDS) items up to Week 8 (acute open-label period)

End point description

End point type

Secondary

End point timeframe

Baseline, up to Week 8

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1197
Units: units on a scale
arithmetic mean (standard deviation)
Work Impairment Score (n=757)	-2.17 ( 2.65 )
Social Life Impairment Score (n=1197)	-2.38 ( 2.85 )
Family Life Impairment Score (n=1197)	-2.16 ( 2.81 )

No statistical analyses for this end point

Secondary: Change from Week 8 in the Sheehan Disability Scale (SDS) items up to Week 20 (stabilization open-label period)

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End point title

Change from Week 8 in the Sheehan Disability Scale (SDS) items up to Week 20 (stabilization open-label period)

End point description

End point type

Secondary

End point timeframe

Week 8, up to Week 20

End point values	LY2216684 + SSRI (stabilization open-label period)
Number of subjects analysed	781
Units: units on a scale
arithmetic mean (standard deviation)
Work Impairment Score (n=567)	-0.58 ( 2.61 )
Social Life Impairment Score (n=781)	-0.47 ( 2.54 )
Family Life Impairment Score (n=781)	-0.5 ( 2.5 )

No statistical analyses for this end point

Secondary: Change from baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 20 (open-label period)

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End point title

Change from baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 20 (open-label period)

End point description

The EQ-5D, a health-related, quality-of-life instrument, contains 2 parts: a health status profile and a visual analog scale (VAS). The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These dimensions are converted into weighted health-state index scores according to United States (US) and United Kingdom (UK) population-based algorithms. The US and UK based index scores range from -0.11 to 1.0 (where a score of 1.0 indicates perfect health) and from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), respectively. The VAS consists of participants rating their current health state from 0 (worst imaginable health state) to 100 (best imaginable health).Analysis population included all randomized pts who have non-missing values at baseline and at least one post-baseline value.LOCF methodology used.

End point type

Secondary

End point timeframe

Baseline, up to Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	779
Units: units on a scale
arithmetic mean (standard deviation)
EQ-5D US (n=773)	0.15 ( 0.19 )
EQ-5D UK (n=773)	0.21 ( 0.29 )
VAS (n=779)	18.07 ( 22.15 )

No statistical analyses for this end point

Secondary: Change from baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 20 (open-label period)

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End point title

Change from baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 20 (open-label period)

End point description

End point type

Secondary

End point timeframe

Baseline, up to Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1167
Units: units on a scale
arithmetic mean (standard deviation)	-6.68 ( 7.03 )

No statistical analyses for this end point

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (open-label period)

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End point title

Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (open-label period)

End point description

The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which included a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present at baseline. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value. All participants who have non-missing values at baseline and at least one post-baseline value.

End point type

Secondary

End point timeframe

Baseline through Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1216
Units: participants
number (not applicable)
TE Suicidal Ideation (n=1216)	66
TE Suicidal Behavior (n=1124)	5

No statistical analyses for this end point

Secondary: Change from baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (open-label period)

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End point title

Change from baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (open-label period)

End point description

End point type

Secondary

End point timeframe

Baseline, up to Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1115
Units: units on a scale
arithmetic mean (standard deviation)	-1.78 ( 4.98 )

No statistical analyses for this end point

Secondary: Change from baseline in blood pressure up to Week 20 (open-label period)

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End point title

Change from baseline in blood pressure up to Week 20 (open-label period)

End point description

Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Analysis population included all randomized participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Baseline, up to Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1214
Units: millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
Systolic blood pressure	2.3 ( 11.95 )
Diastolic blood pressure	2.81 ( 8.63 )

No statistical analyses for this end point

Secondary: Change from randomization in pulse rate at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in pulse rate at Week 44 (double-blind randomized withdrawal period)

End point description

Pulse rate measurements were collected when the participant was in a sitting position. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	291	292
Units: beats per minute (bpm)
least squares mean (standard error)	-2.54 ( 0.74 )	-10.76 ( 0.74 )

No statistical analyses for this end point

Secondary: Change from randomization in blood pressure at Week 44 (double-blind randomized withdrawal period)

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End point title

Change from randomization in blood pressure at Week 44 (double-blind randomized withdrawal period)

End point description

Blood pressure measurements were taken 3 times at each visit in a sitting position. The average of the 3 values was used for analysis. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis which included terms for the fixed categorical effects of treatment, country, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline and baseline-by-visit interaction. Analysis population included all randomized participants who have non-missing values at the time of randomization and at least one post-randomization value.

End point type

Secondary

End point timeframe

Randomization, Week 44

End point values	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)
Number of subjects analysed	291	292
Units: millimeters of mercury (mmHg)
least squares mean (standard error)
Systolic blood pressure	-0.2 ( 0.75 )	-4.19 ( 0.75 )
Diastolic blood pressure	0.24 ( 0.55 )	-4.18 ( 0.55 )

No statistical analyses for this end point

Secondary: Change from baseline in pulse rate up to Week 20 (open-label period)

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End point title

Change from baseline in pulse rate up to Week 20 (open-label period)

End point description

Pulse measurements were collected when the participant was in a sitting position. Analysis population included all randomized participants who have non-missing values at baseline and at least one post-baseline value. Last observation carried forward (LOCF) methodology was used.

End point type

Secondary

End point timeframe

Baseline, up to Week 20

End point values	LY2216684 + SSRI (Acute open-label period)
Number of subjects analysed	1214
Units: beats per minute (bpm)
arithmetic mean (standard deviation)	10.8 ( 12.47 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Entire Study

Adverse event reporting additional description

H9P-MC-LNBN

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

LY2216684 + SSRI (Stabilization Open- label Period)

Reporting group description

Same, stable dose of LY2216684 as in the Acute Open-label Period, orally, once daily (QD) for 12 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all participants who completed the Acute Open-label Period and did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Stabilization Open-label Period.

Reporting group title

LY2216684 + SSRI (Acute Open-label Period)

Reporting group description

Flexible dose of 12 or 18 milligrams (mg) LY2216684, administered orally, once daily (QD) for 8 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all enrolled participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-baseline visit during the Acute Open-label Period.

Reporting group title

LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)

Reporting group description

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who abruptly discontinued LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Reporting group title

Placebo + SSRI (Abrupt Discontinuation Period)

Reporting group description

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who discontinued placebo after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Reporting group title

LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)

Reporting group description

Placebo, orally, once daily (QD) for 2 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all non-randomized participants who discontinued early from either Open-label Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Reporting group title

Placebo + SSRI (Double-blind Randomized Withdrawal Period)

Reporting group description

Placebo, orally, once daily (QD) for 24 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Double-blind Randomized Withdrawal Period.

Reporting group title

LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)

Reporting group description

Same, stable dose of LY2216684 as in the Stabilization Open-label Period, orally, once daily (QD) for 24 weeks, adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes randomized participants who did not discontinue for the reason 'Lost to Follow-up' at the first post-randomization visit during the Double-blind Randomized Withdrawal Period.

Reporting group title

LY2216684 + SSRI (Randomized Tapered Discontinuation Period)

Reporting group description

12 milligrams (mg) LY2216684 for 4 days, 6 mg LY2216684 for 4 days, then placebo for 6 days, orally, once daily (QD), adjunctive to a selective serotonin reuptake inhibitor (SSRI). Includes all randomized participants who tapered discontinuation of LY2216684 after completion of or early withdrawal from the Double-blind Randomized Withdrawal Period and who did not discontinue for the reason 'Lost to Follow-up' at the Discontinuation Period visit.

Serious adverse events	LY2216684 + SSRI (Stabilization Open- label Period)	LY2216684 + SSRI (Acute Open-label Period)	LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)	Placebo + SSRI (Abrupt Discontinuation Period)	LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	LY2216684 + SSRI (Randomized Tapered Discontinuation Period)
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 831 (1.81%)	19 / 1244 (1.53%)	0 / 132 (0.00%)	2 / 267 (0.75%)	8 / 434 (1.84%)	6 / 292 (2.05%)	2 / 294 (0.68%)	2 / 128 (1.56%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
angiomyolipoma
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
breast cancer
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cholesteatoma
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
metastases to liver
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	1 / 267 (0.37%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
hypertension
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	2 / 1244 (0.16%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
hysterectomy
alternative dictionary used: MedDRA 16.1
subjects affected / exposed ^[1]	1 / 641 (0.16%)	0 / 914 (0.00%)	0 / 105 (0.00%)	0 / 212 (0.00%)	0 / 307 (0.00%)	0 / 226 (0.00%)	0 / 223 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
abortion
alternative dictionary used: MedDRA 16.1
subjects affected / exposed ^[2]	1 / 641 (0.16%)	0 / 914 (0.00%)	0 / 105 (0.00%)	0 / 212 (0.00%)	0 / 307 (0.00%)	0 / 226 (0.00%)	0 / 223 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
blighted ovum
alternative dictionary used: MedDRA 16.1
subjects affected / exposed ^[3]	0 / 641 (0.00%)	1 / 914 (0.11%)	0 / 105 (0.00%)	0 / 212 (0.00%)	1 / 307 (0.33%)	0 / 226 (0.00%)	0 / 223 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
chest pain
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
vaginal polyp
alternative dictionary used: MedDRA 16.1
subjects affected / exposed ^[4]	1 / 641 (0.16%)	0 / 914 (0.00%)	0 / 105 (0.00%)	0 / 212 (0.00%)	0 / 307 (0.00%)	0 / 226 (0.00%)	1 / 223 (0.45%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
dyspnoea
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
alcohol abuse
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
depression
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
major depression
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	1 / 128 (0.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
self injurious behaviour
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
suicidal behaviour
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
suicidal ideation
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	1 / 267 (0.37%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
suicide attempt
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	2 / 831 (0.24%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
blood glucose increased
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
intentional overdose
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
poisoning
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
road traffic accident
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
tendon rupture
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	1 / 294 (0.34%)	1 / 128 (0.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
myocardial infarction
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
tachycardia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ventricular extrasystoles
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
convulsion
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
dizziness
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
encephalopathy
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
headache
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypoaesthesia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
syncope
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
colitis ischaemic
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
intestinal obstruction
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
nausea
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	3 / 1244 (0.24%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
oesophageal spasm
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	3 / 1244 (0.24%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
nephrolithiasis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
intervertebral disc disorder
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
osteoarthritis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	1 / 292 (0.34%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
diverticulitis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastroenteritis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	1 / 831 (0.12%)	0 / 1244 (0.00%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
dehydration
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ketosis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	0 / 831 (0.00%)	1 / 1244 (0.08%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	0 / 292 (0.00%)	0 / 294 (0.00%)	0 / 128 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects has been adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects has been adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects has been adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	LY2216684 + SSRI (Stabilization Open- label Period)	LY2216684 + SSRI (Acute Open-label Period)	LY2216684 + SSRI (Randomized Abrupt Discontinuation Period)	Placebo + SSRI (Abrupt Discontinuation Period)	LY2216684 + SSRI (Nonrandomized Abrupt Discontinuation Period)	Placebo + SSRI (Double-blind Randomized Withdrawal Period)	LY2216684 + SSRI (Double-blind Randomized Withdrawal Period)	LY2216684 + SSRI (Randomized Tapered Discontinuation Period)
Total subjects affected by non serious adverse events
subjects affected / exposed	112 / 831 (13.48%)	505 / 1244 (40.59%)	4 / 132 (3.03%)	16 / 267 (5.99%)	32 / 434 (7.37%)	21 / 292 (7.19%)	37 / 294 (12.59%)	9 / 128 (7.03%)
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	8 / 831 (0.96%)	83 / 1244 (6.67%)	1 / 132 (0.76%)	4 / 267 (1.50%)	4 / 434 (0.92%)	4 / 292 (1.37%)	3 / 294 (1.02%)	1 / 128 (0.78%)
occurrences all number	8	86	1	4	4	4	3	1
headache
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	53 / 831 (6.38%)	111 / 1244 (8.92%)	4 / 132 (3.03%)	11 / 267 (4.12%)	24 / 434 (5.53%)	13 / 292 (4.45%)	18 / 294 (6.12%)	7 / 128 (5.47%)
occurrences all number	54	128	5	16	30	13	24	10
Gastrointestinal disorders
constipation
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	14 / 831 (1.68%)	132 / 1244 (10.61%)	0 / 132 (0.00%)	0 / 267 (0.00%)	0 / 434 (0.00%)	2 / 292 (0.68%)	4 / 294 (1.36%)	0 / 128 (0.00%)
occurrences all number	14	134	0	0	0	2	5	0
dry mouth
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	10 / 831 (1.20%)	80 / 1244 (6.43%)	0 / 132 (0.00%)	0 / 267 (0.00%)	1 / 434 (0.23%)	0 / 292 (0.00%)	3 / 294 (1.02%)	0 / 128 (0.00%)
occurrences all number	10	81	0	0	1	0	3	0
nausea
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	18 / 831 (2.17%)	147 / 1244 (11.82%)	1 / 132 (0.76%)	5 / 267 (1.87%)	8 / 434 (1.84%)	5 / 292 (1.71%)	7 / 294 (2.38%)	3 / 128 (2.34%)
occurrences all number	21	155	1	6	10	5	7	3
Skin and subcutaneous tissue disorders
hyperhidrosis
alternative dictionary used: MedDRA 16.1
subjects affected / exposed	23 / 831 (2.77%)	215 / 1244 (17.28%)	0 / 132 (0.00%)	0 / 267 (0.00%)	5 / 434 (1.15%)	1 / 292 (0.34%)	8 / 294 (2.72%)	0 / 128 (0.00%)
occurrences all number	24	228	0	0	5	1	8	0

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/25894953

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Clinical trials

Clinical Trial Results: LY2216684 Compared to Placebo as Adjunctive Therapy to SSRI in the Prevention of Symptom Re-emergence in Major Depressive Disorder

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants who meet criteria for re-emergence of depressive symptoms estimated by Kaplan-Meier product limit method (Double-blind Randomized Withdrawal Period)

Primary: Percentage of Participants who meet criteria for re-emergence of depressive symptoms estimated by Kaplan-Meier product limit method (Double-blind Randomized Withdrawal Period)

Secondary: Percentage of participants with re-emergence of depressive symptoms (Double-blind Randomized Withdrawal Period)

Secondary: Percentage of participants with re-emergence of depressive symptoms (Double-blind Randomized Withdrawal Period)

Secondary: Change from randomization in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Clinical Global Impression of Severity (CGI-S) scores at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Clinical Global Impression of Severity (CGI-S) scores at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores at week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores at week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Sheehan Disability Scale (SDS) items at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Sheehan Disability Scale (SDS) items at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Arizona Sexual Experiences (ASEX) Questionnaire at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 44 (double-blind randomized withdrawal period)

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (double-blind randomized withdrawal period)

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (double-blind randomized withdrawal period)

Secondary: Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 8 (acute open-label period)

Secondary: Change from Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores up to Week 20 (stabilization open-label period)

Secondary: Change from randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from Week 8 in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 20 (stabilization open-label period)

Secondary: Change from baseline in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscale scores up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Clinical Global Impression of Severity (CGI-S) scores up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Clinical Global Impression of Severity (CGI-S) scores up to Week 8 (acute open-label period)

Secondary: Change from Week 8 in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Clinical Global Impression of Severity (CGI-S) scores up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Clinical Global Impression of Severity (CGI-S) scores up to Week 20 (stabilization open-label period)

Secondary: Change from Baseline in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 8 (acute open-label period)

Secondary: Change from Baseline in the Fatigue Associated with Depression (FAsD) average score, experience subscale score, and impact subscale score up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Sheehan Disability Scale (SDS) items up to Week 8 (acute open-label period)

Secondary: Change from baseline in the Sheehan Disability Scale (SDS) items up to Week 8 (acute open-label period)

Secondary: Change from Week 8 in the Sheehan Disability Scale (SDS) items up to Week 20 (stabilization open-label period)

Secondary: Change from Week 8 in the Sheehan Disability Scale (SDS) items up to Week 20 (stabilization open-label period)

Secondary: Change from baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 20 (open-label period)

Secondary: Change from baseline in the EuroQol Questionnaire-5 Dimension (EQ-5D) index scores, visual analog scale up to Week 20 (open-label period)

Secondary: Change from baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 20 (open-label period)

Secondary: Change from baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score at Week 20 (open-label period)

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (open-label period)

Secondary: Number of participants with treatment-emergent suicidal ideation and behaviors assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) (open-label period)

Secondary: Change from baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (open-label period)

Secondary: Change from baseline in the Arizona Sexual Experiences (ASEX) Questionnaire up to Week 20 (open-label period)

Secondary: Change from baseline in blood pressure up to Week 20 (open-label period)

Secondary: Change from baseline in blood pressure up to Week 20 (open-label period)

Secondary: Change from randomization in pulse rate at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in pulse rate at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in blood pressure at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from randomization in blood pressure at Week 44 (double-blind randomized withdrawal period)

Secondary: Change from baseline in pulse rate up to Week 20 (open-label period)

Secondary: Change from baseline in pulse rate up to Week 20 (open-label period)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
LY2216684 Compared to Placebo as Adjunctive Therapy to SSRI in the Prevention of Symptom Re-emergence in Major Depressive Disorder